1. 1 URINARY TRACT INFECTION URINARY TRACT INFECTION URINARY TRACT INFECTION URINARY TRACT INFECTION Dr. Hani Masaadeh MD, Ph.D

2. Urinary tract is normally sterile due to the fact that bacteria moving upwards are regularly washed out by urination Normal flora found in the urethra consist of lactobacillus and staphylococcus to name a few URINARY TRACT INFECTION

3. Second most common infection following respiratory infections UTI occur when bacteria (E. coli) from the digestive tract get into the opening of the urinary tract and multiply Bacteria first infect the urethra, then move to the bladder and finally to the kidneys UTI tend to occur more in women than men

4. URINARY TRACT INFECTION

5. Urinary Tract Infection Upper urinary tract Infections: Pyelonephritis Lower urinary tract infections Cystitis (“traditional” UTI) Urethritis (often sexually-transmitted) Prostatitis

6. Symptoms of Urinary Tract Infection Dysuria Increased frequency Hematuria Fever Nausea/Vomiting (pyelonephritis) Flank pain (pyelonephritis)

7. Findings on Exam in UTI Physical Exam: CVA tenderness (pyelonephritis) Urethral discharge (urethritis) Tender prostate on DRE (prostatitis) Labs: Urinalysis + leukocyte esterase + nitrites More likely gram-negative rods + WBCs + RBCs

8. Culture in UTI Positive Urine Culture = >10 5 CFU/mL Most common pathogen for cystitis, prostatitis, pyelonephritis: Escherichia coli Staphylococcus saprophyticus Proteus mirabilis Klebsiella Enterococcus Most common pathogen for urethritis Chlamydia trachomatis Neisseria Gonorrhea

9. Lower Urinary Tract Infection - Cystitis Uncomplicated (Simple) cystitis In healthy woman, with no signs of systemic disease Complicated cystitis In men, or woman with comorbid medical problems. Recurrent cystitis

10. Uncomplicated (simple) Cystitis Definition Healthy adult woman (over age 12) Non-pregnant No fever, nausea, vomiting, flank pain Diagnosis Dipstick urinalysis (no culture or lab tests needed) Treatment Trimethroprim/Sulfamethoxazole for 3 days May use fluoroquinolone (ciprofoxacin or levofloxacin) in patient with sulfa allergy, areas with high rates of bactrim- resistance Risk factors: Sexual intercourse May recommend post-coital voiding or prophylactic antibiotic use.

11. Complicated Cystitis Definition Females with comorbid medical conditions All male patients Indwelling foley catheters Urosepsis/hospitalization Diagnosis Urinalysis, Urine culture Further labs, if appropriate. Treatment Fluoroquinolone (or other broad spectrum antibiotic) 7-14 days of treatment (depending on severity) May treat even longer (2-4 weeks) in males with UTI

12. Special cases of Complicated cystitis Indwelling foley catheter Try to get rid of foley if possible! Only treat patient when symptomatic (fever, dysuria) Leukocytes on urinalysis Patient’s with indwelling catheters are frequently colonized with great deal of bacteria. Should change foley before obtaining culture, if possible Candiduria Frequently occurs in patients with indwelling foley. If grows in urine, try to get rid of foley! Treat only if symptomatic. If need to treat, give fluconazole (amphotericin if resistance)

13. Recurrent Cystitis Want to make sure urine culture and sensitivity obtained. May consider urologic work-up to evaluate for anatomical abnormality. Treat for 7-14 days.

14. Pyelonephritis Infection of the kidney Associated with constitutional symptoms – fever, nausea, vomiting, headache Diagnosis: Urinalysis, urine culture, CBC, Chemistry Treatment: 2-weeks of Trimethroprim/sulfamethoxazole or fluoroquinolone Hospitalization and IV antibiotics if patient unable to take po. Complications: Perinephric/Renal abscess: Suspect in patient who is not improving on antibiotic therapy. Diagnosis: CT with contrast, renal ultrasound May need surgical drainage. Nephrolithiasis with UTI Suspect in patient with severe flank pain Need urology consult for treatment of kidney stone

15. Prostatitis Symptoms: Pain in the perineum, lower abdomen, testicles, penis, and with ejaculation, bladder irritation, bladder outlet obstruction, and sometimes blood in the semen Diagnosis: Typical clinical history (fevers, chills, dysuria, malaise, myalgias, pelvic/perineal pain, cloudy urine) The finding of an edematous and tender prostate on physical examination Will have an increased PSA Urinalysis, urine culture Treatment: Trimethoprim/sulfamethoxazole, fluroquinolone or other broad spectrum antibiotic 4-6 weeks of treatment Risk Factors: Trauma Sexual abstinence Dehydration

16. Importance of Urinary Tract Infections is demonstrated by the fact that 20% of women between ages 20-65 suffer one attack per year Approximately 50% of women develop a UTI during their lives and there is a prevalence rate of 5% per year of asymptomatic or covert bacteriuria in non- pregnant women between ages 21 and 65 URINARY TRACT INFECTION

17. TYPES LOWER TRACT INFECTIONUPPER TRACT INFECTION URETHRITIS PROSTATITIS CYSTITIS PYELONEPHRITIS PERI NEPHRIC ABSCESS

18. URINARY TRACT INFECTION AETIOLOGY Background 1.Bacterial infections of urinary tract are a very common reason to seek health services 2.Common in young females and uncommon in males under age 50 3.Common causative organisms Escherichia coli (gram-negative enteral bacteria) causes most community acquired infections Staphylococcus saprophyticus, gram-positive organism causes 10 – 15% Catheter-associated UTI’s caused by gram-negative bacteria: Proteus, Klebsiella, Seratia, Pseudomonas

19. URINARY TRACT INFECTION CLINICAL PRESENTATION Cystitis dysuria (burning or discomfort on urination) frequency nocturia suprapubic discomfort

20. Urine is sterile Presence of inflammatory cells or pathogens in urine indicate a urinary tract infection (UTI) managed in general medical practice Up to 50% of women will have a UTI at some point in their life UTI uncommon in men except over the age of 60 when urinary tract obstruction due to prostatic hypertrophy may occur

21. Urinary System Infections Serious problem in hospitals Cause morbidity Pathogens can travel up the ureters and reach the kidneys UTIs are named according the place of infection ‐ In the urethra = Urethritis ‐ In the bladder = Cystitis ‐ In the kidneys = Nephritis ‐ In the prostate (men) = prostatitis Majority of infections are caused by bacteria, though some are fungal

22. Urine is an excellent culture medium for bacteria Bacteria entering the bladder from the external environment or blood passing through the renal artery can normally be flushed out during urination Infections occur when bacteria get into the urine and remain More easily in women because of a shorter urethra and absence of bacteriostatic prostatic secretions (as in men) Catheterisation may also introduce organisms into the bladder

23. 23 Causative agents: mainly faecal bacteria Community - acquired Escherichia coli Proteus mirabilis Klebsiella pneumoniae Enterococcus faecalis Staphylococcus species Hospital –acquired Pseudomonas aeruginosa Candida albicans AND (community acquired) Mycobacterium tuberculosis (renal TB – will be a ‘sterile pyuria’

24. Urinary Tract Infection (UTI) Cystitis 1.Most common UTI 2.Remains superficial, involving bladder mucosa, which becomes hyperemic and may hemorrhage 3.General manifestations of cystitis a.Dysuria b.Frequency and urgency c.Nocturia d.Urine has foul odor, cloudy (pyuria), bloody (hematuria) e.Suprapubic pain and tenderness 4.Older clients may present with different manifestations a.Nocturia, incontinence b.Confusion c.Behavioral changes d.Lethargy e.Anorexia f.Fever or hypothermia

25. Urinary Tract Infection (UTI) Pyelonephritis 1.Inflammation of renal pelvis and parenchyma (functional kidney tissue) 2.Acute pyelonephritis a.Results from an infection that ascends to kidney from lower urinary tract Risk factors 1.Pregnancy 2.Urinary tract obstruction and congenital malformation 3.Urinary tract trauma, scarring 4.Renal calculi 5.Polycystic or hypertensive renal disease 6.Chronic diseases, i.e. diabetes mellitus 7.Vesicourethral reflux

26. Urinary Tract Infection (UTI) Diagnostic Tests a.Urinalysis: assess pyuria, bacteria, blood cells in urine; Bacterial count >100,000 /ml indicative of infection b.Rapid tests for bacteria in urine 1.Nitrite dipstick (turning pink = presence of bacteria) 2.Leukocyte esterase test (identifies WBC in urine) c.Gram stain of urine: identify by shape and characteristic (gram positive or negative); obtain by clean catch urine or catheterization

27. Urinary Tract Infection (UTI) d.Urine culture and sensitivity: identify infecting organism and most effective antibiotic; culture requires 24 – 72 hours for results; obtain by clean catch urine or catheterization e.WBC with differential: leukocytosis and increased number of neutraphils

28. URINARY TRACT INFECTION PATHOGENESIS BACTERIA GET ACCESS FROM URETHRA AND ASCENDS FEMALES ARE MORE PRONE DUE TO: SMALL URETHRA GRAM NEGATIVE ORGANISM RADIATE FROM PERI ANAL AREA TO URETHRA SEXUAL INTERCOURSE SUSCEPTIBILITY OF EPITHELIUM

29. URINARY TRACT INFECTION PATHOGENESIS FEMALE SEX AND INTERCOURSE PREDISPOSES PREGNANCY: URETERAL TONE AND URETHRAL PERISTALSIS DECREASES OBSTRUCTION IN FREE FLOW OF URINE: TUMOR, STRICTURE, CALCULI AND BPH ETC. CATHETERISATION, URETHRAL DILATATION, CYSTOSCOPY

30. URINARY TRACT INFECTION PATHOGENESIS The normal bladder is capable of clearing itself of organisms within 2 to 3 days of their introduction. Defense mechanisms (1) the elimination of bacteria by voiding (2) the antibacterial properties of urine and its constituents (3) the intrinsic mucosal bladder defense mechanisms (4) an acid vaginal environment (female) (5) prostatic secretions (male)

31. URINARY TRACT INFECTION PATHOGENESIS Two potential routes : (1) the hematogenous route, with seeding of the kidney during the course of bacteremia (2) the ascending route, from the urethra to the bladder, then from the bladder to the kidneys via the ureters.

32. URINARY TRACT INFECTION PATHOGENESIS Hematogenous Infection Because the kidneys receive 20% to 25% of the cardiac output, any microorganism that reaches the bloodstream can be delivered to the kidneys. The major causes of hematogenous infection are S. aureus, Salmonella species, P. aeruginosa, and Candida species.

33. URINARY TRACT INFECTION PATHOGENESIS Hematogenous Infection Chronic infections (skin, respiratory tract) blood circulation kidney (cortex) small abscess renal tubular renal pelvis renal papillary

34. URINARY TRACT INFECTION PATHOGENESIS ASCENDING INFECTION The ability of host defense Urinary tract mucosal cells damaged The power of bacterial adhesions(toxicity) organisms urethra,periurethral tissues bladder ureters renal pelvis renal medulla

35. URINARY TRACT INFECTION PATHOGENESIS Voiding dysfunction is characterized by some or all of the following: urgency frequency dysuria hesitancy dribbling of urine overt incontinence secondary to a UTI or to local irritants such as pinworm infestation

36. URINARY TRACT INFECTION HISTORY AND PHYSICAL EXAMINATION Age-related Risk Factors for UTI Advanced Age Fecal incontinence/impaction Incomplete bladder emptying or neurogenic bladder Vaginal atrophy/estrogen deficiency Pelvic prolapse/cystocele Insufficient fluid intake/dehydration Indwelling foley catheter or urinary catheterization or instrumentation procedures

37. URINARY TRACT INFECTION CLINICAL PRESENTATION Uncomplicated Cystitis Urethritis Female >>> male Sequel rare

38. URINARY TRACT INFECTION CLINICAL PRESENTATION Complicated Pyelonephritis Prostate obstruction Relapse +++

39. URINARY TRACT INFECTION CLINICAL PRESENTATION Fever with chill & rigor Haematuria Strangury Ineffectual desire Cloudy urine Offensive urine Pain lower abdomen

40. 40 Investigation: the specimen Mid-stream Urine (MSU) is the specimen of choice Suprapubic urine Catheter urine In all cases, urine must be examined immediately or stored at 4 o C Contamination of urine is a big problem!! Should also determine the site of infection

41. 41 Diagnosis Urine culture yielding greater than 100,000 colony- forming units (10 5 CFU) per ml = significant bacteriuria. However, 30% or more of symptomatic women have CFU counts below this level Therefore, urine cultures are no longer advocated – pyuria (slide/dipstick) Leukocyte esterase test - sensitivity of 75-90% pyuria associated UTI Dipstick test for nitrite a surrogate marker for bacteriuria - not all uropathogens reduce nitrates to nitrite Gram stains of urine can be used to detect bacteriuria - time-consuming and has low sensitivity

42. 42 Standard procedures Investigation of UTI involves the detection of bacteriuria together with evidence of an inflammatory response Microscopy for pyuria and haematuria (can also reveal other structures, e.g. crystals, other cells, casts) Culture for detection of bacteria Sensitivity testing to advise on antibiotic treatment

43. 43 Microscopy Not always performed as it is time consuming The finding of a rise in WBCs (pyuria) should be linked to a bacteriuria May also see RBCs (haematuria); this is potentially an important finding Microtitre plate and an inverted microscope enables many urines to be simply screened

44. 44 White cells in urine In normal state, there is a continuous secretion of WBCs into urine In a UTI caused by bacteria, neutrophils may be secreted in large numbers Labs may report >200/μl (>200 x 10 3 /ml) and will suggest this as significant pyuria Lower numbers: < 10 3 /ml are regarded as not significant

45. 45 Culture: procedure Cystitis is usually caused by a single species of bacterium present at >10 5 /ml Standard loopful of urine is streaked onto a selective medium, e.g. CLED Typically 1μl Incubate overnight and count the colonies If a genuine UTI, should see >100 colonies; this = >100 bacteria/μl or >10 5 /ml

46. 46 Culture: interpretation >10 5 /ml of a single species strongly suggests a UTI 10 4 -10 5 /ml of a single species is equivocal – needs repeat specimen for testing <10 4 /ml is regarded as no significant growth >1 species in any numbers suggests contamination Catheter and suprapubic urines should be interpreted differently

47. 47 Sensitivity testing Clinical isolates are tested against antibiotics that –a) are filtered by kidneys –b) are usually effective against common agents Since UTIs are common, drugs should be cheap! Typical course of treatment: 5-7 days orally, resulting in sterile urine Nitrofurantoin, nalidixic acid, trimethoprim, ampicillin + gentamicin, cephalosporins

48. 48 Antibiotic sensitivities

49. URINARY TRACT INFECTION TREATMENT FLUID ++ ALKALI EMPTYING OF BLADDER HYGIENE

50. Classification of U.T.I. Recurrent U.T.I.s that are reinfection. Isolated infections Recurrent infections resulting from bacterial persistence. Unresolved infection